决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:The role of T-cells in head and neck squamous cell carcinoma: From immunity to immunotherapy.
手术、放疗和/或化疗是标准治疗,但 5 年总生存期不足 50%。
头颈部鳞状细胞癌(HNSCC)是一组复杂肿瘤,影响上呼吸消化道。主要危险因素与烟草和酒精摄入密切相关,HPV感染也常有关联。标准治疗为手术、放疗和/或化疗,但5年总生存率低于50%。基因组学、分子医学、免疫学和纳米技术进展增进了对肿瘤生物学的认识,有助于临床研究者开发疗效更好、毒性更低的治疗方法。头颈部肿瘤具有多种免疫逃逸机制,包括调节免疫检查点以减弱免疫应答,以及募集并诱导抑制性免疫细胞分化。对HNSCC生物学及其与肿瘤微环境强相互作用的认识,凸显免疫调节药物的作用。近期对肿瘤免疫学特征的认识推动了有效生物标志物发现,可更好筛选可能通过免疫治疗改善总生存的患者。特别包括免疫检查点抑制抗体相关标志物,如抗PD-1/PD-L1和抗CTLA-4抗体,无论与标准疗法联合还是单药使用。CAR-T细胞和纳米颗粒等头颈癌新型免疫疗法受到关注;本文讨论识别癌细胞T细胞靶点以生成CAR-T细胞的必要性,同时强调评估此类疗法特异性和安全性的重要性。
Head and neck squamous cell carcinoma (HNSCC) encompass a group of complex entities of tumours affecting the aerodigestive upper tract. The main risk factors are strongly related to tobacco and alcohol consumption, but also HPV infection is often associated. Surgery, radiotherapy and/or chemotherapy are the standard treatments, though the 5-year overall survival is less than 50%. The advances in genomics, molecular medicine, immunology, and nanotechnology have shed a light on tumour biology which helps clinical researchers to obtain more efficacious and less toxic therapies. Head and neck tumours possess different immune escape mechanisms including diminishing the immune response through modulating immune checkpoints, in addition to the recruitment and differentiation of suppressive immune cells. The insights into the HNSCC biology and its strong interaction with the tumour microenvironment highlights the role of immunomodulating agents. Recently, the knowledge of the immunological features of these tumours has paved the way for the discovery of effective biomarkers that allow a better selection of patients with odds of improving overall survival through immunotherapy. Specially biomarkers regarding immune checkpoint inhibitors antibodies, such as anti-PD-1/PD-L1 and anti-CTLA-4 in combination with standard therapy or as monotherapy. New immunotherapies to treat head and neck cancer carcinomas, such as CAR T cells and nanoparticles have been the center of attention and in this review, we discuss the necessity of finding targets for the T cell in the cancer cells to generate CAR T cells, but also the relevance of evaluating specificity and safety of those therapies.
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